The long term objective of this research is to characterize the biological roles of 1-0-hexadecyl-2-acetyl-sn-glyceryl-3- phosphorylcholine (AGEPC) as a mediator of inflammation. The proposed studies will focus upon the potent vasoactive properties of AGEPC, and upon its production during acute inflammation in vivo. It has been documented in experimental animals that 1 pmole or less of AGEPC induces increased vascular permeability and leukocyte infiltrates; also, vasoconstriction and microvasclar injury can occur with higher AGEPC doses. Furthermore, documented production of AGEPC in vitro by neutrophils, eosinophils, basophils, monocytes, macrophages, and even endothelial cells suggests that cellular infiltrates of various inflammatory processes produce sufficient AGEPC to initiate both the vasoactive and leukotactic events of acute inflammation. However, recent studies indicate that the microvascular alterations due to locally produced AGEPC may be influenced by certain aspects of pathophysiology in inflamed tissue including production of biologically potent eicosanoids that can modulate AGEPC-induced vascular responses, adhesion of AGEPC-activated leukocytes that may obstruct microvascular flow, degredation of AGEPC in tissue by plasma or cell derived enzymes, production of heterogeneous acetylated alkyl phosphoglycerides that may alter receptor and enzyme binding by virtue of their close structural similarity to AGEPC, and possible desensitization of the microvasculature to AGEPC. Therefore, the proposed studies will utilize both histologic and a combination of biochemical and physiologic observations, primarily in the rat and the guinea pig, to accomplish the following: 1) further examine the morphologic features of immediate nd prolonged AGEPC-induced microvascular alterations in cremaster muscle and skin; 2) characterize the synthesis of AGEPC and other acetylated alkyl phosphoglycerides in specific types of inflammatory skin lesions; 3) investigate the roles of leukocytes and plasma enzymes in restricting the vasoactive effects of AGEPC. It is hoped that these studies will provide new information regarding the role of AGEPC as a mediator of acute inflammation.